The extracellular matrices of bones and teeth that give these unique tissues their shape and strength are synthesized and maintained throughout life by highly specialized cells. The cell's ability to assemble, mineralize and maintain the matrices is generally thought to be modulated through a variety of noncollagenous proteins (NCP). The goal of this project is to study the structure and function of several of these noncollagenous proteins. We have completed the cloning and sequencing of human and certain useful animal model noncollagenous proteins including bone sialoprotein (BSP), osteopontin (OPN), decorin (DCN), and biglycan (BGN). The human biglycan gene has been sequenced and localized to the end of the long arm of the X chromosome. The human decorin gene has recently been cloned, mapped and partially sequenced. The intron-exon structure of decorin and biglycan are identical, thus supporting our original hypothesis that the two are a direct consequence of gene duplication and divergent evolution. The DCN gene is located at 12q21.3. We have continued to be successful producing monospecific antisera to all of the major NCP in human and several animal model systems. In collaboration with Dr. Paolo Bianco, we have used both the antisera and cDNA probes to begin studies on the developmental pattern of expression of these proteins in human and rodent models. Production of the mg quantities of nondenatured protein necessary for structure-function studies has been successful for rat BSP. We have preliminary evidence for a cryptic cell attachment domain other than the ArgGlyAsp (RGD) tripeptide typical of the integrin-binding class of receptors, and have recently proposed that this second site may be homologous to the second attachment site of fibrinogen.